The primary objective is to study the inhibitory effects of selenium (Na2Se03) on the colon carcinogen, 1,2-dimethylhydrazine. Initially the acute toxicology of selenium as sodium selenite will be determined. Using these data the doses of selenium will be selected for the chronic toxicology and carcinogenicity studies. All animal studies will use male Sprague-Dawley rats. Selenium will be provided ad libitum in the drinking water before, during and/or after carcinogen administration. The rats will receive weekly subcutaneous injections of 20 mg DMH per Kg body weight for 10 and 20 weeks. In a recent publication we have reported the colon tumor incidence in DMH-treated rats for 20 weeks was reduced from 87% to 40% by 4 ppm selenium in the drinking water. Additionally the total number of colon tumors induced by DMH was reduced more than three-fold by supplemental selenium. In the proposed study we wish to determine whether: 1) pre-exposure to selenium delays the onset of tumors, 2) early stages of colon cancer induction can be inhibited by sellnium, 3) colon cancer induction can be reversed by selenium, and 4) Sister Chromatid Exchanges (SCE's) can be used to distinguish lymphocyte cultures from normal, DMH treated and DMH plus selenium treated rats. The answers to these questions will be explored using the combined methods of gross and histopathological examination, enzymatic and cytogenetic assays. Colonic tissue assays will include glutathione peroxidase, selenium, mucin changes, ATPase, Beta-glucuronidase and mixed function oxidase activities. In blood, selenium, glutathione peroxidase, SGPT, alkaline phosphatase, and Sister Chromatid Exchange (SCE) levels will be measured. Perhaps these multidisciplined analyses may provide potential markers for diagnosis of neoplastic condition of the large bowel.